Makindo Medical Notes

Related Subjects: |Herpes Varicella-Zoster (Shingles) Infection |Chickenpox Varicella Infection |Varicella Cerebral Vasculopathy |Herpes Viruses |Herpes Zoster Ophthalmicus (HZO) Shingles |MonkeyPox |Mumps |Measles |Rubella (German Measles) |Epstein-Barr Virus infection |Cytomegalovirus (CMV) infections |CMV retinitis infections |Toxoplasmosis

Treat suspected HSVE with IV Aciclovir if it is included in the differential diagnosis. HSVE can cause focal neurological deficits and may closely resemble a middle cerebral artery (MCA) infarct in patients who otherwise appear well. Clues to HSVE include fever, a history of cold sores, MRI changes, seizures, confusion, clouding of consciousness, and progression. HSVE occurs approximately once in every 3000 stroke cases, which means the diagnosis is often delayed. A typical stroke unit may encounter one case of HSVE as a stroke mimic every 5–10 years.

About

• Herpes simplex encephalitis is the most serious form of HSVE.
• Other viral causes include West Nile virus.

Epidemiology

• Incidence: approximately 1 case per million per year.
• In the UK, there are around 50–100 cases annually.
• About half of cases occur in individuals over the age of 50, which translates to 25–50 cases in that age group in the UK each year.
• Many patients present late with coma and florid clinical signs.
• Others may present with stroke-like symptoms that later deteriorate.
• Assuming half of cases present as stroke-like, this equates to approximately 12–25 cases presenting as stroke mimics out of the 100,000 strokes that occur annually in the UK.

Virology

• Herpes simplex virus type 1 (HSV-1) encephalitis is more common in adults.
• Herpes simplex virus type 2 (HSV-2) infection is more common in neonates.

Aetiology

• 90% of individuals are seropositive for HSV-1, indicating past exposure.
• HSV infects nasopharyngeal cells and enters the sensory branch of the lingual nerve, ascending to the trigeminal ganglion, where it remains latent for life.
• Reactivation can occur due to factors such as immunosuppression, trauma, or stress.
• HSV-1 has a predilection for the temporal lobes, and to a lesser extent, the frontal lobes.
• It invades brain parenchyma, causing hemorrhagic necrosis and, in severe cases, fulminant hemorrhagic necrotising encephalitis.
• Limbic system involvement is common, with bilateral but asymmetric involvement.

Reactivation Causes: May present with cold sores

• Trauma
• Sunlight exposure (e.g., recent sun holiday)
• Immunosuppression
• X-ray irradiation
• Physical or psychological stress
• Pneumococcal infection
• Meningococcal infection
• Menstruation

Pathology

• Hemorrhagic necrosis typically affects the inferomedial portion of the temporal lobe.
• The disease often starts unilaterally and then spreads to the contralateral temporal lobe.

Clinical Features

• Headache, fever, and both focal and generalised seizures.
• Presence of cold sores on the lips or mouth.
• Altered consciousness and abnormalities of speech and behavior.
• Hyperreflexia, hemiparesis, and, in severe cases, coma.

Investigations

• Full Blood Count (FBC): May show elevated white cell count (WCC).
• Urea & Electrolytes (U&E): Hyponatraemia is seen in 50% of HSVE cases but also occurs in about 35% of strokes.
• CT/MRI Brain: Used to exclude abscesses. Imaging may show lesions in the temporal lobes, including necrosis and hemorrhage.
• Cerebrospinal Fluid (CSF) analysis: Raised lymphocytes and elevated protein. Bloody CSF can lead to a false-negative polymerase chain reaction (PCR) due to interference by porphyrins.
• Viral PCR: HSV PCR is critical for diagnosis; other tests, such as enterovirus PCR or West Nile virus (WNV) testing, may be required if indicated.
• MRI Brain: Typically shows asymmetrical temporal lobe changes, including inflammation, swelling, and necrosis. Restricted diffusion due to cytotoxic oedema is common but less intense than in infarction.
• EEG: May show slowing and periodic discharges.
• Brain Biopsy: Neuronal inclusion bodies (Cowdry Type A) may be seen in the nuclei of infected neurons in HSVE.

Poor Prognostic Indicators

• Age > 30 years
• Coma at presentation
• Bilateral EEG abnormalities
• High CNS viral load
• Treatment delayed beyond 4 days
• Abnormal CT scan

Differential Diagnosis

• In immunosuppressed patients, consider Cytomegalovirus (CMV) infection, which may require treatment with Ganciclovir.

Management

• If there is any suspicion of HSVE, initiate treatment with IV Aciclovir immediately, even before confirmation. Untreated HSVE can be fatal.
• The threshold for initiating treatment should be low. Studies have shown that mortality is significantly reduced in Aciclovir-treated patients (28% versus 54%). However, even with early treatment, mortality remains around 30%, and long-term neurological deficits are common.
• IV Aciclovir: 10 mg/kg three times daily for 2–3 weeks.
• Monitor renal function closely during treatment, and ensure proper hydration and, if necessary, NG feeding.
• Patients are often managed in a High Dependency Unit (HDU) setting. Long-term neurological sequelae are common in survivors.
• There is no current evidence supporting the use of steroids. Manage seizures as needed.
• For the most severe cases, hemicraniectomy may be required for decompression.

Late Complications

• Long-term sequelae are seen in approximately half of treated patients, including poor memory, emotional lability, poor concentration, irritability, and depression.

References

• Herpes simplex encephalitis - JNNP
• Herpes encephalitis: A stroke mimicker